Candidate: The candidate, Frank A. Dinenno, Ph.D., is a physiologist currently supported by an individual NRSA from NIA. Dr. Dinenno's previous and current research focus has been on sympathetic neural control of the circulation, with specific emphasis on how these control mechanisms are modulated by advancing age and regular physical activity in humans. His immediate goal is to acquire new research and professional skills to better prepare and help him achieve his long-term goal of developing a successful independent extramurally-funded research program on aging and cardiovascular function. This proposed KO1 should provide Dr. Dinenno the necessary training to achieve his goal. Career Development Plan: Dr. Dinenno's research career development training activities will consist of (1) acquiring new research skills associated with and complimentary to the proposed research plan; and (2) structured research- and professional skills-related activities. Environment: The environment for Dr. Dinenno's training will be outstanding. The Sponsor (Dr. Joyner) and consulting mentors are engaged in biomedical research and are extramurally-funded from NIH. All are established scientists with strong records of successful mentoring in biomedical research, three of the six are experts in aging research. Support from the General Clinical Research Center will enhance the training environment. Research: The following specific aims will be addressed: 1) to determine whether whole-leg alpha-adrenergic receptor responsiveness is reduced with age under resting conditions in healthy humans, and whether this is specific for cq- or c2-adrenergic receptors; (2) to determine whether the ability to blunt-adrenergic vasoconstriction during large muscle dynamic exercise is impaired in older adults and (3) whether this impairment is due to age-related reductions in nitric oxide bioavailability mediated via elevations in oxidative stress; and (4) to determine whether a program of regular aerobic exercise improves the ability of previously sedentary older adults to blunt sympathetic vasoconstriction at rest and during exercise. The expected results should yield new information regarding sympathetic neural control of the circulation at rest and during exercise in aging humans, and the intervention study should yield novel information about training-induced adaptations and peripheral circulatory control in older adults.